tbuckley/cabot-search huggingface dataset:
Association of Prehospital Needle Decompression With Mortality Among Injured Patients Requiring Emergency Chest Decompression
Authors: Daniel Muchnok, Allison Vargo, Andrew-Paul Deeb, Francis X. Guyette, Joshua B. Brown
Journal: JAMA Surgery (2022)

Prehospital needle decompression (PHND) is a rare but potentially life-saving procedure. Prior studies on chest decompression in trauma patients have been small, limited to single institutions or emergency medical services (EMS) agencies, and lacked appropriate comparator groups, making the effectiveness of this intervention uncertain.To determine the association of PHND with early mortality in patients requiring emergent chest decompression.This was a retrospective cohort study conducted from January 1, 2000, to March 18, 2020, using the Pennsylvania Trauma Outcomes Study database. Patients older than 15 years who were transported from the scene of injury were included in the analysis. Data were analyzed between April 28, 2021, and September 18, 2021.Patients without PHND but undergoing tube thoracostomy within 15 minutes of arrival at the trauma center were the comparison group that may have benefited from PHND.Mixed-effect logistic regression was used to determine the variability in PHND between patient and EMS agency factors, as well as the association between risk-adjusted 24-hour mortality and PHND, accounting for clustering by center and year. Propensity score matching, instrumental variable analysis using EMS agency-level PHND proportion, and several sensitivity analyses were performed to address potential bias.A total of 8469 patients were included in this study; 1337 patients (11%) had PHND (median [IQR] age, 37 [25-52] years; 1096 male patients [82.0%]), and 7132 patients (84.2%) had emergent tube thoracostomy (median [IQR] age, 32 [23-48] years; 6083 male patients [85.3%]). PHND rates were stable over the study period between 0.2% and 0.5%. Patient factors accounted for 43% of the variation in PHND rates, whereas EMS agency accounted for 57% of the variation. PHND was associated with a 25% decrease in odds of 24-hour mortality (odds ratio [OR], 0.75; 95% CI, 0.61-0.94; P = .01). Similar results were found in patients who survived their ED stay (OR, 0.68; 95% CI, 0.52-0.89; P < .01), excluding severe traumatic brain injury (OR, 0.65; 95% CI, 0.45-0.95; P = .03), and restricted to patients with severe chest injury (OR, 0.72; 95% CI, 0.55-0.93; P = .01). PHND was also associated with lower odds of 24-hour mortality after propensity matching (OR, 0.79; 95% CI, 0.62-0.98; P = .04) when restricting matches to the same EMS agency (OR, 0.74; 95% CI, 0.56-0.99; P = .04) and in instrumental variable probit regression (coefficient, -0.60; 95% CI, -1.04 to -0.16; P < .01).In this cohort study, PHND was associated with lower 24-hour mortality compared with emergent trauma center chest tube placement in trauma patients. Although performed rarely, PHND can be a life-saving intervention and should be reinforced in EMS education for appropriately selected trauma patients.
Pharmacologic Inhibition of NT5C2 Reverses Genetic and Nongenetic Drivers of 6-MP Resistance in Acute Lymphoblastic Leukemia
Authors: Clara Reglero, Chelsea L. Dieck, Arie Zask, Farhad Forouhar, Anouchka P. Laurent, Wen-Hsuan W. Lin, Robert Albero, Hannah I. Miller, Cindy Ma, Julie M. Gastier-Foster, Mignon L. Loh, Liang Tong, Brent R. Stockwell, Teresa Palomero, Adolfo A. Ferrando
Journal: Cancer Discovery (2022)

Low-intensity maintenance therapy with 6-mercaptopurine (6-MP) limits the occurrence of acute lymphoblastic leukemia (ALL) relapse and is central to the success of multiagent chemotherapy protocols. Activating mutations in the 5'-nucleotidase cytosolic II (NT5C2) gene drive resistance to 6-MP in over 35% of early relapse ALL cases. Here we identify CRCD2 as a first-in-class small-molecule NT5C2 nucleotidase inhibitor broadly active against leukemias bearing highly prevalent relapse-associated mutant forms of NT5C2 in vitro and in vivo. Importantly, CRCD2 treatment also enhanced the cytotoxic activity of 6-MP in NT5C2 wild-type leukemias, leading to the identification of NT5C2 Ser502 phosphorylation as a novel NT5C2-mediated mechanism of 6-MP resistance in this disease. These results uncover an unanticipated role of nongenetic NT5C2 activation as a driver of 6-MP resistance in ALL and demonstrate the potential of NT5C2 inhibitor therapy for enhancing the efficacy of thiopurine maintenance therapy and overcoming resistance at relapse. Relapse-associated NT5C2 mutations directly contribute to relapse in ALL by driving resistance to chemotherapy with 6-MP. Pharmacologic inhibition of NT5C2 with CRCD2, a first-in-class nucleotidase inhibitor, enhances the cytotoxic effects of 6-MP and effectively reverses thiopurine resistance mediated by genetic and nongenetic mechanisms of NT5C2 activation in ALL. This article is highlighted in the In This Issue feature, p. 2483.
An 18-Year-Old Woman With Recurrent Skin, Nail, and Oral Mucosal Abnormalities
Authors: Zhaoyuan Wang, Xiaoyong Man
Journal: JAMA (2022)

An 18-year-old woman had a 14-year history of recurrent skin, nail, and oral mucosal abnormalities, treated with 3- to 6-month courses of itraconazole; the abnormalities typically recurred within 6 to 12 months of discontinuing itraconazole. Skin scrapings from the lower extremities demonstrated fungal elements; fungal culture of the skin scrapings grew Candida albicans . What is the diagnosis and what would you do next?
Range of Risk Factor Levels, Risk Control, and Temporal Trends for Nephropathy and End-stage Kidney Disease in Patients With Type 1 and Type 2 Diabetes
Authors: Janita Halminen, Naveed Sattar, Araz Rawshani, Björn Eliasson, Katarina Eeg-Olofsson, Deepak L. Bhatt, Aidin Rawshani
Journal: Diabetes Care (2022)

OBJECTIVE To investigate trends, optimal levels for cardiometabolic risk factors, and multifactorial risk control in diabetic nephropathy and end-stage kidney disease (ESKD) in patients with diabetes and matched control subjects. RESEARCH DESIGN AND METHODS This study included 701,622 patients with diabetes from the Swedish National Diabetes Register and 2,738,137 control subjects. Trends were analyzed with standardized incidence rates. Cox regression was used to assess excess risk, optimal risk factor levels, and risk according to the number of risk factors, in diabetes. RESULTS ESKD incidence among patients with and without diabetes initially declined until 2007 and increased thereafter, whereas diabetic nephropathy decreased throughout follow-up. In patients with diabetes, baseline values for glycated hemoglobin, systolic blood pressure (SBP), triglycerides, and BMI were associated with outcomes. Hazard ratio (HR) for ESKD for patients with type 2 diabetes who had all included risk factors at target was 1.60 (95% CI 1.49–1.71) compared with control subjects and for patients with type 1 diabetes 6.10 (95% CI 4.69–7.93). Risk for outcomes increased in a stepwise fashion for each risk factor not at target. Excess risk for ESKD in type 2 diabetes showed a HR of 2.32 (95% CI 2.30–2.35) and in type 1 diabetes 10.92 (95% CI 10.15–11.75), compared with control. CONCLUSIONS Incidence of diabetic nephropathy has declined substantially, whereas ESKD incidence has increased. Traditional and modifiable risk factors below target levels were associated with lower risks for outcomes, particularly notable for the causal risk factors of SBP and HbA1c, with potential implications for care.
Primary Care Physician Use and Frequency of Visits Among Physicians in Ontario, Canada
Authors: Emily Rhodes, Claire Kendall, Robert Talarico, Elizabeth Muggah, Caroline Gerin-Lajoie, Christopher Simon, Taylor McFadden, Daniel Myran, Manish M. Sood, Peter Tanuseputro
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Maintaining a healthy physician workforce includes the routine use of primary care physician (PCP) services; however, physicians may face barriers to attaining formal care. <h3>Objective</h3> To analyze access to and frequency of visits to PCPs among physicians compared with nonphysicians. <h3>Design, Setting, and Participants</h3> This population-based, retrospective cohort study used registration data from the College of Physicians and Surgeons of Ontario, Canada, from January 1, 1990, to March 31, 2018. Data for all newly practicing physicians as of March 31, 2018, were linked to Ontario health administrative databases. Data were analyzed from August 25, 2020, to August 6, 2021. <h3>Main Outcomes and Measures</h3> The main outcomes were enrollment in a PCP practice and visits with a PCP. Generalized estimating equations compared primary care visits between physicians and nonphysicians, matched 1:5 based on age, sex, neighborhood income quintile, and health region. <h3>Results</h3> Among 19 581 physicians (mean [SD] age, 43.99 [8.94] years; 53.27% male) matched to 97 905 nonphysicians, physicians were less likely to be enrolled with a PCP than were nonphysicians (81.8% vs 86.4%; absolute difference, 4.6%; adjusted odds ratio [OR], 0.75; 95% CI, 0.72-0.79) and had fewer primary care visits during the preceding 2 years (median [IQR], 2 [0-4] vs 4 [1-7]; adjusted relative rate ratio [RRR], 0.59; 95% CI, 0.58-0.60). Physicians aged 40 years or older and male physicians were less likely to be rostered (ages 40-44 years: OR, 0.70 [95% CI, 0.64-0.77]; male: OR, 0.60 [95% CI, 0.57-0.63]) and more likely to have a lower frequency of PCP visits (ages 40-44 years: RRR, 0.53 [95% CI, 0.51-0.56]; male: RRR, 0.50 [95% CI, 0.50-0.51]) compared with nonphysicians. <h3>Conclusions and Relevance</h3> In this retrospective cohort study, enrollment with a PCP practice and frequency of visits were lower among physicians compared with a matched general population of nonphysicians. Individual, system, and medical cultural factors associated with these results need to be better understood so that physicians can take better care of themselves and their patients.
Analysis of Specialty Nephrology Care Among Patients With Chronic Kidney Disease and High Risk of Disease Progression
Authors: Maggie Wang, Samson S. Peter, Chi D. Chu, Delphine S. Tuot, Jonathan H. Chen
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Identification of patients with chronic kidney disease (CKD) with high risk of progression to kidney failure can help ensure they receive appropriate and effective nephrology care. <h3>Objective</h3> To examine whether patients with CKD at various levels of kidney failure risk receive nephrology care within 1 year of established risk. <h3>Design, Setting, and Participants</h3> This population-based, retrospective cohort study collected nationwide administrative health claims data from 156 733 adult patients who met the Kidney Disease: Improving Global Outcomes initiative CKD diagnostic criteria between January 1, 2012, and December 31, 2019, and had an available urine albumin to creatinine ratio within 90 days of a serum creatinine laboratory test. Patients with a history of dialysis or kidney transplant, a prior visit with a nephrologist in the past year, or palliative care billing codes or those who died or disenrolled within 1 year of the albumin to creatinine ratio measurement were excluded. Data analysis was performed from September 10, 2022, to February 14, 2022. <h3>Exposures</h3> Kidney failure risk computed with the 5-year Kidney Failure Risk Equation. <h3>Main Outcomes and Measures</h3> The main outcome was nephrology care rates across tiers of kidney failure risk, estimated as the proportion of individuals having a nephrologist visit within 1 year after index time. <h3>Results</h3> The study population consisted of 156 733 patients with CKD (mean [SD] age, 74.6 [8.4] years; 91 906 [58.6%] female; 86 457 [55.2%] White). A total of 106 004 patients (67.6%) had a low (≤1%) 5-year risk of kidney failure. Nephrology visit rates increased with higher kidney failure risk. Among the 137 highest-risk patients, 79 (57.7%; 95% CI, 48.4%-64.7%) had a nephrology visit. Among 7730 patients with risk above a 10% threshold, 3208 (41.5%; 95% CI, 40.3%-42.4%) had a nephrology visit. <h3>Conclusions and Relevance</h3> This study's findings suggest that nearly half of patients with CKD at high risk of progressing to kidney failure do not have a nephrologist visit within 1 year of established risk. These findings have implications in the design of risk-based guidelines for referral and in the practice of delivering nephrology care to patients with CKD.
Regulatory considerations to keep pace with innovation in digital health products
Authors: John Torous, Ariel D. Stern, Florence T. Bourgeois
Journal: npj Digital Medicine (2022)

Abstract Rapid innovation and proliferation of software as a medical device have accelerated the clinical use of digital technologies across a wide array of medical conditions. Current regulatory pathways were developed for traditional (hardware) medical devices and offer a useful structure, but the evolution of digital devices requires concomitant innovation in regulatory approaches to maximize the potential benefits of these emerging technologies. A number of specific adaptations could strengthen current regulatory oversight while promoting ongoing innovation.
Association of Diet and Physical Activity With All-Cause Mortality Among Adults With Parkinson Disease
Authors: Xinyuan Zhang, Samantha A. Molsberry, Michael A. Schwarzschild, Alberto Ascherio, Xiang Gao
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Greater diet quality and physical activity level are associated with a lower risk of developing Parkinson disease (PD). However, information regarding the association between lifestyle behaviors and survival after PD diagnosis remains limited. <h3>Objective</h3> To examine the association of prediagnosis and postdiagnosis overall diet quality and physical activity with all-cause mortality among individuals with PD. <h3>Design, Setting, and Participants</h3> This population-based cohort study analyzed male participants in the Health Professionals Follow-up Study from 1986 to 2012 and female participants in the Nurses' Health Study from 1984 to 2012. Participants who were diagnosed with PD and had complete baseline dietary assessment data were included. Data were analyzed from January 2021 to February 2022. <h3>Exposures</h3> Prediagnosis diet quality, assessed by the Alternative Healthy Eating Index (AHEI), and physical activity, assessed by metabolic equivalent task (MET) hours per week reported on questionnaires, were the primary exposures of interest to minimize reverse causation. <h3>Main Outcomes and Measures</h3> Mortality, which was followed up until 2018, was the primary outcome. Cox proportional hazards regression models were used to estimate the association of diet and physical activity with mortality individually and jointly, and the models were adjusted for age, total energy intake, caffeine intake, and other lifestyle risk factors. <h3>Results</h3> The sample comprised 1251 individuals with PD, which included 652 men (52.1%) with a median (IQR) age at diagnosis of 73.4 (67.5-78.7) years. During the 32 to 34 years of follow-up, 942 participants died. The adjusted hazard ratio (HR) comparing the highest vs the lowest AHEI quartile was 0.69 (95% CI, 0.56- 0.85) for prediagnosis analyses and 0.57 (95% CI, 0.42-0.78) for postdiagnosis analyses. Similar results were obtained for cumulative mean MET hours per week in the prediagnosis analyses (HR, 0.71; 95% CI, 0.57-0.87) and postdiagnosis analyses (HR, 0.47; 95% CI, 0.35-0.63). The inverse association persisted for PD-specific mortality (postdiagnosis AHEI: HR, 0.52 [95% CI, 0.33-0.80]; postdiagnosis physical activity: HR, 0.37 [95% CI, 0.25-0.55]). In the joint analyses of diet quality and physical activity before the PD diagnosis, the adjusted HR was 0.51 (95% CI, 0.36-0.73) for individuals in the highest vs lowest tertiles for both variables. The HR for diet quality and physical activity after the diagnosis was 0.35 (95% CI, 0.23-0.52). <h3>Conclusions and Relevance</h3> Results of this study showed that a healthy dietary pattern and an active lifestyle were associated with a lower rate of all-cause mortality among individuals with PD. Consuming a healthy diet and engaging in physical activity or exercise could be targeted to improve PD outcomes.
High-Contact Object and Surface Contamination in a Household of Persons with <i>Monkeypox Virus</i> Infection — Utah, June 2022
Authors: Jack A. Pfeiffer, Abigail Collingwood, Linda E. Rider, Faisal S. Minhaj, Audrey M. Matheny, Chantal Kling, Andrea M. McCollum, Leisha D. Nolen, Clint N. Morgan
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

In May 2022, the Salt Lake County Health Department reported two real-time polymerase chain reaction (PCR)-confirmed travel-associated cases of monkeypox to the Utah Department of Health and Human Services (UDHHS). The two persons with monkeypox (patients A and B) lived together without other housemates. Both persons experienced prodromal symptoms (e.g., fatigue and body aches). Eight days after symptom onset, patient A experienced penile lesions; lesions spread to the lips, hands, legs, chest, and scalp by day 10. Patient B experienced prodromal symptoms 8 days after illness onset of patient A; patient B experienced a lesion on the foot which spread to the leg and finger by day 11. Although both patients had lesions in multiple anatomic areas, the overall number of lesions was small, and lesions varied in presentation from "pimple-like" or ulcerated, to characteristically well-circumscribed and centrally umbilicated. Both patients had mild illness. The time from symptom onset to resolution was approximately 30 days for patient A and approximately 22 days for patient B.
Trends in Prescribing Preferences for Antidiabetic Medications Among Patients With Type 2 Diabetes in the U.K. With and Without Chronic Kidney Disease, 2006–2020
Authors: Julia Liaw, Meera Harhay, Soko Setoguchi, Tobias Gerhard, Chintan V. Dave
Journal: Diabetes Care (2022)

To evaluate trends in antidiabetic medication initiation patterns among patients with type 2 diabetes mellitus (T2DM) with and without chronic kidney disease (CKD).A retrospective cohort study using the UK Clinical Practice Research Datalink (2006-2020) was conducted to evaluate the overall, first-, and second line (after metformin) medication initiation patterns among patients with CKD (n = 38,622) and those without CKD (n = 230,963) who had T2DM.Relative to other glucose-lowering therapies, metformin initiations declined overall but remained the first-line treatment of choice for both patients with and those without CKD. Sodium-glucose cotransporter-2 (SGLT2i) use increased modestly among patients with CKD, but this increase was more pronounced among patients without CKD; by 2020, patients without CKD, compared with patients with CKD, were three (28.5% vs. 9.4%) and six (46.3% vs. 7.9%) times more likely to initiate SGLT2i overall and as second-line therapy, respectively. Glucagon-like peptide 1 receptor agonist (GLP-1RA) use was minimal regardless of CKD status (<5%), whereas both dipeptidyl peptidase-4 inhibitor (DPP4i) and sulfonylurea use remained high among patients with CKD. For instance, by 2020, and among patients with CKD, DPP4i and sulfonylureas constituted 28.3% and 20.6% of all initiations, and 57.4% and 30.3% of second-line initiations, respectively.SGLT2i use increased among patients with T2DM, but this increase was largely driven by patients without CKD. Work is needed to identify barriers associated with the uptake of therapies with proven cardiorenal benefits (e.g., SGLT2i, GLP-1RA) among patients with CKD.
Treatment of Tic Douloureux by Percutaneous Retrogasserian Glycerol Injection
Authors: L. Dade Lunsford
Journal: JAMA (1982)

Thirty patients with tic douloureux underwent treatment by percutaneous retrogasserian glycerol injection (PRGI). All patients had symptomatic trigeminal neuralgia refractory to medical therapy. Fifteen patients had recurrent tic after one to four prior operations. The technique was simple to perform and required no intraoperative physiological testing or short-acting barbiturate supplementation during transovale placement of a spinal needle in the trigeminal cistern of Meckel's cave. Precise placement of small volumes (0.15 to 0.35 mL) of sterile glycerol was ensured by first demonstrating the anatomy of the trigeminal cistern using metrizamide. Overall, 23 patients have remained pain free five to 12 months after treatment. Nineteen patients had no change in facial sensation after injection. Treatment by PRGI is a valid alternative therapy for tic douloureux, with the additional benefit of a much-reduced incidence of facial sensory loss when compared with differential thermal rhizotomy by a radiofrequency-induced lesion technique. Facial deafferentation is not mandatory for successful percutaneous treatment of tic douloureux. (<i>JAMA</i>1982;248:449-453)
Longitudinal single-cell transcriptomics reveals distinct patterns of recurrence in acute myeloid leukemia
Authors: Yanan Zhai, Prashant Singh, Anna Dolnik, Peter Brazda, Nader Atlasy, Nunzio del Gaudio, Konstanze Döhner, Hartmut Döhner, Saverio Minucci, Joost Martens, Lucia Altucci, Wout Megchelenbrink, Lars Bullinger, Hendrik G. Stunnenberg
Journal: Molecular Cancer (2022)

Abstract Background Acute myeloid leukemia (AML) is a heterogeneous and aggressive blood cancer that results from diverse genetic aberrations in the hematopoietic stem or progenitor cells (HSPCs) leading to the expansion of blasts in the hematopoietic system. The heterogeneity and evolution of cancer blasts can render therapeutic interventions ineffective in a yet poorly understood patient-specific manner. In this study, we investigated the clonal heterogeneity of diagnosis (Dx) and relapse (Re) pairs at genetic and transcriptional levels, and unveiled the underlying pathways and genes contributing to recurrence. Methods Whole-exome sequencing was used to detect somatic mutations and large copy number variations (CNVs). Single cell RNA-seq was performed to investigate the clonal heterogeneity between Dx-Re pairs and amongst patients. Results scRNA-seq analysis revealed extensive expression differences between patients and Dx-Re pairs, even for those with the same -presumed- initiating events. Transcriptional differences between and within patients are associated with clonal composition and evolution, with the most striking differences in patients that gained large-scale copy number variations at relapse. These differences appear to have significant molecular implications, exemplified by a DNMT3A/FLT3-ITD patient where the leukemia switched from an AP-1 regulated clone at Dx to a mTOR signaling driven clone at Re. The two distinct AML1-ETO pairs share genes related to hematopoietic stem cell maintenance and cell migration suggesting that the Re leukemic stem cell-like (LSC-like) cells evolved from the Dx cells. Conclusions In summary, the single cell RNA data underpinned the tumor heterogeneity not only amongst patient blasts with similar initiating mutations but also between each Dx-Re pair. Our results suggest alternatively and currently unappreciated and unexplored mechanisms leading to therapeutic resistance and AML recurrence.
Quotational and Reference Accuracy in Surgical Journals
Authors: James T. Evans
Journal: JAMA (1990)

Fifty randomly selected references from a single monthly issue of The<i>American Journal of Surgery; Surgery, Gynecology and Obstetrics; and Surgery</i>were evaluated for citation and quotation errors. Thirteen major and 41 minor citation errors were found in the three journals. Thirty-seven major quotation errors were identified. The data support the hypothesis that authors do not check their references or may not even read them. This hypothesis may be expanded to maintain that reviewers do not check references. (<i>JAMA</i>. 1990;263:1353-1354)